Gene and immunohistochemical expression of HIF-1α, GLUT-1, FASN, and adipophilin in carcinoma ex pleomorphic adenoma development
João Figueira Scarini
Oral Diagnosis Department, Piracicaba Dental School/UNICAMP, Piracicaba, Brazil
Search for more papers by this authorLarissa Fernandes Rosa
Pathology Department, Faculty of Medical Sciences/UNICAMP, Campinas, Brazil
Search for more papers by this authorReydson Alcides de Lima Souza
Oral Diagnosis Department, Piracicaba Dental School/UNICAMP, Piracicaba, Brazil
Search for more papers by this authorErika Said Abu Egal
Pathology Department, Faculty of Medical Sciences/UNICAMP, Campinas, Brazil
Search for more papers by this authorAlfio José Tincani
Head and Neck Surgery Department, Faculty of Medical Sciences/UNICAMP, Campinas, Brazil
Search for more papers by this authorAntônio Santos Martins
Head and Neck Surgery Department, Faculty of Medical Sciences/UNICAMP, Campinas, Brazil
Search for more papers by this authorLuiz Paulo Kowalski
Head and Neck Surgery Department, AC Camargo Cancer Center, São Paulo, Brazil
Search for more papers by this authorEdgard Graner
Oral Diagnosis Department, Piracicaba Dental School/UNICAMP, Piracicaba, Brazil
Search for more papers by this authorRicardo Della Coletta
Oral Diagnosis Department, Piracicaba Dental School/UNICAMP, Piracicaba, Brazil
Search for more papers by this authorRoman Carlos
Oral and Maxillofacial Pathology Laboratory, Head and Neck Clinical Center, Guatemala City, Guatemala
Search for more papers by this authorRogério de Oliveira Gondak
Department of Pathology, Federal University of Santa Catarina (UFSC), Florianópolis, Brazil
Search for more papers by this authorOslei Paes de Almeida
Oral Diagnosis Department, Piracicaba Dental School/UNICAMP, Piracicaba, Brazil
Search for more papers by this authorAlbina Messias de Almeida Milani Altemani
Pathology Department, Faculty of Medical Sciences/UNICAMP, Campinas, Brazil
Search for more papers by this authorDébora Campanella Bastos
Oral Diagnosis Department, Piracicaba Dental School/UNICAMP, Piracicaba, Brazil
Search for more papers by this authorCorresponding Author
Fernanda Viviane Mariano
Pathology Department, Faculty of Medical Sciences/UNICAMP, Campinas, Brazil
Correspondence
Fernanda Viviane Mariano, Pathology Department, Faculty of Medical Sciences/ University of Campinas, Av. Tessália Vieira de Camargo, 126 – Barão Geraldo, Cidade Universitária, 13083-887 Campinas, São Paulo, Brazil.
Email: [email protected]
Search for more papers by this authorJoão Figueira Scarini
Oral Diagnosis Department, Piracicaba Dental School/UNICAMP, Piracicaba, Brazil
Search for more papers by this authorLarissa Fernandes Rosa
Pathology Department, Faculty of Medical Sciences/UNICAMP, Campinas, Brazil
Search for more papers by this authorReydson Alcides de Lima Souza
Oral Diagnosis Department, Piracicaba Dental School/UNICAMP, Piracicaba, Brazil
Search for more papers by this authorErika Said Abu Egal
Pathology Department, Faculty of Medical Sciences/UNICAMP, Campinas, Brazil
Search for more papers by this authorAlfio José Tincani
Head and Neck Surgery Department, Faculty of Medical Sciences/UNICAMP, Campinas, Brazil
Search for more papers by this authorAntônio Santos Martins
Head and Neck Surgery Department, Faculty of Medical Sciences/UNICAMP, Campinas, Brazil
Search for more papers by this authorLuiz Paulo Kowalski
Head and Neck Surgery Department, AC Camargo Cancer Center, São Paulo, Brazil
Search for more papers by this authorEdgard Graner
Oral Diagnosis Department, Piracicaba Dental School/UNICAMP, Piracicaba, Brazil
Search for more papers by this authorRicardo Della Coletta
Oral Diagnosis Department, Piracicaba Dental School/UNICAMP, Piracicaba, Brazil
Search for more papers by this authorRoman Carlos
Oral and Maxillofacial Pathology Laboratory, Head and Neck Clinical Center, Guatemala City, Guatemala
Search for more papers by this authorRogério de Oliveira Gondak
Department of Pathology, Federal University of Santa Catarina (UFSC), Florianópolis, Brazil
Search for more papers by this authorOslei Paes de Almeida
Oral Diagnosis Department, Piracicaba Dental School/UNICAMP, Piracicaba, Brazil
Search for more papers by this authorAlbina Messias de Almeida Milani Altemani
Pathology Department, Faculty of Medical Sciences/UNICAMP, Campinas, Brazil
Search for more papers by this authorDébora Campanella Bastos
Oral Diagnosis Department, Piracicaba Dental School/UNICAMP, Piracicaba, Brazil
Search for more papers by this authorCorresponding Author
Fernanda Viviane Mariano
Pathology Department, Faculty of Medical Sciences/UNICAMP, Campinas, Brazil
Correspondence
Fernanda Viviane Mariano, Pathology Department, Faculty of Medical Sciences/ University of Campinas, Av. Tessália Vieira de Camargo, 126 – Barão Geraldo, Cidade Universitária, 13083-887 Campinas, São Paulo, Brazil.
Email: [email protected]
Search for more papers by this authorAbstract
Objective
To analyze the gene and immunohistochemical expression of HIF-1α, GLUT-1, FASN, and adipophilin in normal salivary gland (NSG), pleomorphic adenoma (PA), and carcinoma ex pleomorphic adenoma (CXPA) samples.
Material and Methods
The gene expression was investigated by the real-time PCR (qRT-PCR) method in 9 samples of frozen tissues of normal salivary gland, 13 PA, and 10 CXPA. We validated the reactions by immunohistochemistry on 20 samples from NSG, 85 PA, and 44 CXPA.
Results
Our results showed that there was no statistically significant difference in HIF-1α gene and immunohistochemistry expression among the tissues studied while FASN gene and immunohistochemistry expression increased along the carcinogenesis of the PA. GLUT-1 was significantly more expressed in tumor tissues (PA and CXPA), although protein is mainly expressed in transformed cells than in PA and NSG. In contrast, adipophilin was significantly more expressed in NSG while the expression of the protein increased in PA and CXPA.
Conclusions
In summary, the data presented here suggest that neoplastic cells reprogram the expression of GLUT-1 and adipophilin to adapt to the tumor microenvironment and reinforce, through immunohistochemical results, a possible transcriptional and post-translational regulatory mechanisms that act on the expression of these genes.
CONFLICTS OF INTEREST
All authors have declared no conflicts of interest.
Supporting Information
| Filename | Description |
|---|---|
| odi13332-sup-0001-TableS1.docxWord document, 26.8 KB | Table S1 |
| odi13332-sup-0002-TableS2.docxWord document, 24 KB | Table S2 |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
REFERENCES
- Ambrosio, M. R., Piccaluga, P. P., Ponzoni, M., Rocca, B. J., Malagnino, V., Onorati, M., … Lazzi, S. (2012). The alteration of lipid metabolism in Burkitt lymphoma identifies a novel marker: Adipophilin. PLoS ONE, 7(8), e44315. https://doi.org/10.1371/journal.pone.0044315
- Barron, C. C., Bilan, P. J., Tsakiridis, T., & Tsiani, E. (2016). Facilitative glucose transporters: Implications for cancer detection, prognosis and treatment. Metabolism, 65(2), 124–139. https://doi.org/10.1016/j.metabol.2015.10.007
- Bauerschlag, D. O., Maass, N., Leonhardt, P., Verburg, F. A., Pecks, U., Zeppernick, F., … Bräutigam, K. (2015). Fatty acid synthase overexpression: Target for therapy and reversal of chemoresistance in ovarian cancer. Journal of Translational Medicine, 13, 146. https://doi.org/10.1186/s12967-015-0511-3
- Bell, D., Bullerdiek, J., Gnepp, D. R., Schwartz, M. R., Stenman, G., & Triantafyllou, A. (2017). Pleomorphic adenoma. In A. K. El-Naggar, J. K. C. Chan, J. R. Grandis, T. Takata, & P. J. Slootweg (Eds.), WHO classification head and neck tumours, 4th ed . (pp. 185–186). Lyon, France: IARC.
- Bensaad, K., Favaro, E., Lewis, C. A., Peck, B., Lord, S., Collins, J. M., … Harris, A. L. (2014). Fatty acid uptake and lipid storage induced by HIF-1α contribute to cell growth and survival after hypoxia-reoxygenation. Cell Reports, 9(1), 349–365. https://doi.org/10.1016/j.celrep.2014.08.056
- Brasaemle, D. L. (2007). Thematic review series: Adipocyte biology. The perilipin family of structural lipid droplet proteins: Stabilization of lipid droplets and control of lipolysis. Journal of Lipid Research, 48(12), 2547–2559. https://doi.org/10.1194/jlr.R700014-JLR200
- Burns, J. S., & Manda, G. (2017). Metabolic pathways of the Warburg effect in health and disease: Perspectives of choice, chain or chance. International Journal of Molecular Sciences, 18(12), E2755. https://doi.org/10.3390/ijms18122755
- Cao, Q., Ruan, H., Wang, K., Song, Z., Bao, L., Xu, T., … Zhang, X. (2018). Overexpression of PLIN2 is a prognostic marker and attenuates tumor progression in clear cell renal cell carcinoma. International Journal of Oncology, 53(1), 137–147. https://doi.org/10.3892/ijo.2018.4384
- Cardoso, C. M., de Jesus, S. F., de Souza, M. G., Santos, E. M., Santos, C. K. C., Silveira, C. M., … Guimarães, A. L. S. (2019). Is HIF1-a deregulated in malignant salivary neoplasms? Gene, 701, 41–45. https://doi.org/10.1016/j.gene.2019.03.017
- Chen, C., Pore, N., Behrooz, A., Ismail-Beigi, F., & Maity, A. (2001). Regulation of glut1 mRNA by hypoxia-inducible factor-1. Interaction between H-ras and hypoxia. Journal of Biological Chemistry, 276(12), 9519–9525.
- Costa, A. F., Tasso, M. G., Mariano, F. V., Soares, A. B., Chone, C. T., Crespo, A. N., … Altemani, A. (2012). Levels and patterns of expression of hypoxia-inducible factor-1α, vascular endothelial growth factor, glucose transporter-1 and CD105 in adenoid cystic carcinomas with high-grade transformation. Histopathology, 60(5), 816–825. https://doi.org/10.1111/j.1365-2559.2011.04128.x
- Demasi, A. P., Costa, A. F., Altemani, A., Furuse, C., Araújo, N. S., & Araújo, V. C. (2010). Glucose transporter protein 1 expression in mucoepidermoid carcinoma of salivary gland: Correlation with grade of malignancy. International Journal of Experimental Pathology, 91(2), 107–113. https://doi.org/10.1111/j.1365-2613.2009.00702.x
- Díaz, K. P., Gondak, R., Martins, L. L., de Almeida, O. P., León, J. E., Mariano, F. V., … Vargas, P. A. (2019). Fatty acid synthase and Ki-67 immunoexpression can be useful for the identification of malignant component in carcinoma ex-pleomorphic adenoma. Journal of Oral Pathology & Medicine, 48(3), 232–238. https://doi.org/10.1111/jop.12820
- dos Santos, H. T., Silva, R. N., Piña, A. R., de Souza do Nascimento, J., de Almeida, O. P., Egal, E. S. A., … Altemani, A. (2016). Lipid droplets are involved in the process of high-grade transformation of adenoid cystic carcinoma. Histopathology, 69(1), 160–162. https://doi.org/10.1111/his.12916
- A. K. El-Naggar, J. K. C. Chan, J. R. Grandis, T. Takata, & P. J. Slootweg eds. WHO classification head and neck Tumours, 4th ed. Lyon, France: IARC.
- Eveson, J. W., & Cawson, R. A. (1985). Salivary gland tumours. A review of 2410 cases with particular reference to histological types, site, age and sex distribution. The Journal of Pathology, 146(1), 51–58. https://doi.org/10.1002/path.1711460106
- Fiorentzis, M., Kalirai, H., Katopodis, P., & Coupland, S. E. (2017). Adipophilin expression in primary and metastatic uveal melanoma: A pilot study. Graefe’s Archive Clinical and Experimental Ophthalmology, 255(5), 1049–1051. https://doi.org/10.1007/s00417-017-3630-0
- Flavin, R., Peluso, S., Nguyen, P. L., & Loda, M. (2010). Fatty acid synthase as a potential therapeutic target in cancer. Future Oncology, 6(4), 551–562. https://doi.org/10.2217/fon.10.11
- Fujimoto, M., Matsuzaki, I., Yamamoto, Y., Yoshizawa, A., Warigaya, K., Iwahashi, Y., … Murata, S. I. (2016). Adipophilin expression in cutaneous malignant melanoma. Journal of Cutaneous Pathology, 44(3), 228–236. https://doi.org/10.1111/cup.12868
- Koppenol, W. H., Bounds, P. L., & Dang, C. V. (2011). Otto Warburg's contributions to current concepts of cancer metabolism. Nature Reviews Cancer, 11(5), 325–337. https://doi.org/10.1038/nrc3038
- Kujan, O., Shearston, K., & Farah, C. S. (2017). The role of hypoxia in oral cancer and potentially malignant disorders: A review. Journal of Oral Pathology & Medicine, 46(4), 246–252. https://doi.org/10.1111/jop.12488
- Matsubara, J., Honda, K., Ono, M., Sekine, S., Tanaka, Y., Kobayashi, M., … Yamada, T. (2011). Identification of adipophilin as a potential plasma biomarker for colorectal cancer using label-free quantitative mass spectrometry and protein microarray. Cancer Epidemiology Biomarkers & Prevention, 20(10), 2195–2203. https://doi.org/10.1158/1055-9965.EPI-11-0400
- Menendez, J. A., & Lupu, R. (2007). Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis. Nature Reviews Cancer, 7(10), 763–777.
- Röhrig, F., & Schulze, A. (2016). The multifaceted roles of fatty acid synthesis in cancer. Nature Reviews Cancer, 16(11), 732–749. https://doi.org/10.1038/nrc.2016.89
- Saarikoski, S. T., Rivera, S. P., & Hankinson, O. (2002). Mitogen-inducible gene 6 (MIG-6), adipophilin and tuftelin are inducible by hypoxia. FEBS Letters, 530(1–3), 186–190. https://doi.org/10.1016/s0014-5793(02)03475-0
- Schito, L., & Semenza, G. L. (2016). Hypoxia-inducible factors: Master regulators of cancer progression. Trends in Cancer, 2(12), 758–770. https://doi.org/10.1016/j.trecan.2016.10.016
- Sedassari, B. T., Rodrigues, M. F. S. D., Conceição, T. S., Mariano, F. V., Alves, V. A. F., Nunes, F. D., … de Souza, S. C. O. M. (2017). Increased SOX2 expression in salivary gland carcinoma ex pleomorphic adenoma progression: An association with adverse outcome. Virchows Archiv, 471(6), 775–784. https://doi.org/10.1007/s00428-017-2220-1
- Singh, K., Agarwal, C., Pujani, M., Verma, P., & Chauhan, V. (2017). Carcinoma ex pleomorphic adenoma: A diagnostic challenge on cytology. Diagnostic Cytopathology, 45(7), 651–654. https://doi.org/10.1002/dc.23704
- Song, J. B., Morrissey, J. J., Mobley, J. M., Figenshau, K. G., Vetter, J. M., Bhayani, S. B., … Figenshau, R. S. (2019). Urinary aquaporin 1 and perilipin 2: Can these novel markers accurately characterize small renal masses and help guide patient management? International Journal of Urology, 26(2), 260–265. https://doi.org/10.1111/iju.13854
- Speight, P. M., & Barrett, A. W. (2002). Salivary gland tumours. Oral Diseases, 8(5), 229–240.
- Tolkach, Y., Lüders, C., Meller, S., Jung, K., Stephan, C., & Kristiansen, G. (2017). Adipophilin as prognostic biomarker in clear cell renal cell carcinoma. Oncotarget, 8(17), 28672–28682. https://doi.org/10.18632/oncotarget.15639
- Wang, G. L., & Semenza, G. L. (1993). Characterization of hypoxia-inducible factor 1 and regulation of DNA binding activity by hypoxia. Journal of Biological Chemistry, 268(29), 21513–21518.
- Warburg, O., Posener, K., & Negelein, E. (1924). Über den stoffwechsel der Carcinomzelle. Naturwissenschaften, 152, 319–344.
- Westhoff, C. C., Mrozinski, J., Riedel, I., Heid, H. W., & Moll, R. (2017). Perilipin 1 is a highly specific marker for adipocytic differentiation in sarcomas with intermediate sensitivity. Journal of Cancer Research and Clinical Oncology, 143(2), 225–232. https://doi.org/10.1007/s00432-016-2263-8
- Wijffels, K. I., Hoogsteen, I. J., Lok, J., Rijken, P. F., Marres, H. A., de Wilde, P. C., … Kaanders, J. H. (2009). No detectable hypoxia in malignant salivary gland tumors: Preliminary results. International Journal of Radiation Oncology, Biology, Physics, 73(5), 1319–1325. https://doi.org/10.1016/j.ijrobp.2008.06.1927
- Zadra, G., Ribeiro, C. F., Chetta, P., Ho, Y., Cacciatore, S., Gao, X., … Loda, M. (2019). Inhibition of de novo lipogenesis targets androgen receptor signaling in castration-resistant prostate cancer. Proceedings of the National Academy of Sciences of the United States of America, 116(2), 631–640. https://doi.org/10.1073/pnas.1808834116
- Zhang, X. D., Li, W., Zhang, N., Hou, Y. L., Niu, Z. Q., Zhong, Y. J., … Yang, S. Y. (2014). Identification of adipophilin as a potential diagnostic tumor marker for lung adenocarcinoma. International Journal of Clinical and Experimental Medicine, 7(4), 1190–1196.
- Zoula, S., Hérigault, G., Ziegler, A., Farion, R., Décorps, M., & Rémy, C. (2003). Correlation between the occurrence of 1H-MRS lipid signal, necrosis and lipid droplets during C6 rat glioma development. NMR in Biomedicine, 16(4), 199–212. https://doi.org/10.1002/nbm.831
